Molecular recognition is at the heart of biology and many biotechnological applications. If cheap and robust synthetic receptors can be prepared for arbitrarily selected drugs, carbohydrate, or oligopeptides, numerous new technologies and biomedical tools will become possible. Improved drug analysis, extraction of drugs or biomolecules from their natural milieu, novel sensors, intervention of biomolecular recognition, and replacing expensive antibodies in affinity chromatography are but some of the possibilities enabled by such antibody-mimicking materials. Molecular imprinting is a powerful way of making synthetic receptors. Although molecularly imprinted polymers, sometimes referred to as plastic antibodies, have found applications in chemical and biological sensing, enzyme-like catalysis, and separation, there are significant challenges facing this technology, including heterogeneous binding sites, low percentage of high-affinity binding sites, incomplete template removal, and difficulty in imprinting in water. The overall objective of this proposal is to fill he gap in the knowledge by developing protein-mimicking molecularly imprinted receptors for a broad range of biologically interesting molecules. The proposed molecularly imprinted nanoparticles (MINPs) can be prepared and purified in 2-3 days without any special techniques, as long as the cross- linkable surfactants and other cross-linkers are available. The MINP receptors, typically 3-5 nm in diameter, resemble proteins in size, hydrophilic exterior, and tailored hydrophobic binding pockets in the core, but easily tolerate long-term storage, high temperatures, and organic solvents due to their heavy cross-linking. The proposed research will lead to robust synthetic receptors for a wide range of biologically interesting guests including hydrophobic drugs, carbohydrates, and oligopeptides. Fundamental structure-activity relationship for these biomimetic receptors will be established through the investigation. The research is expected to open up numerous opportunities for chemists, biologists, engineers, and clinicians in the future as cheap synthetic antibodies become readily available.

Public Health Relevance

The proposed research aims to develop antibody-mimicking synthetic receptors for a broad range of biologically interesting molecules. If cheap and robust synthetic receptors can be prepared for arbitrarily selected drugs, carbohydrate, oligopeptides, or other biologically important entities, numerous new biotechnologies and biomedical tools will become possible. Improved drug analysis, facile extraction of drugs or biomolecules from their natural milieu, novel sensors, intervention of biomolecular recognition, and replacing expensive antibodies in affinity chromatography are but some of the possibilities enabled by such receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM113883-03
Application #
9318568
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2015-08-15
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Iowa State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011
Fa, Shixin; Zhao, Yan (2018) Water-Soluble Nanoparticle Receptors Supramolecularly Coded for Acidic Peptides. Chemistry 24:150-158
Duan, Likun; Zhao, Yan (2018) Selective Binding of Folic Acid and Derivatives by Imprinted Nanoparticle Receptors in Water. Bioconjug Chem 29:1438-1445
Zhao, Yan (2018) Sequence-Selective Recognition of Peptides in Aqueous Solution: A Supramolecular Approach through Micellar Imprinting. Chemistry 24:14001-14009
Awino, Joseph K; Gunasekara, Roshan W; Zhao, Yan (2017) Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding. J Am Chem Soc 139:2188-2191
Gunasekara, Roshan W; Zhao, Yan (2017) A General Method for Selective Recognition of Monosaccharides and Oligosaccharides in Water. J Am Chem Soc 139:829-835
Fa, Shixin; Zhao, Yan (2017) Peptide-Binding Nanoparticle Materials with Tailored Recognition sites for Basic Peptides. Chem Mater 29:9284-9291
Awino, Joseph K; Zhao, Yan (2017) Imprinted micelles for chiral recognition in water: shape, depth, and number of recognition sites. Org Biomol Chem 15:4851-4858
Awino, Joseph K; Gunasekara, Roshan W; Zhao, Yan (2016) Selective Recognition of d-Aldohexoses in Water by Boronic Acid-Functionalized, Molecularly Imprinted Cross-Linked Micelles. J Am Chem Soc 138:9759-62
Awino, Joseph K; Hu, Lan; Zhao, Yan (2016) Molecularly Responsive Binding through Co-occupation of Binding Space: A Lock-Key Story. Org Lett 18:1650-3
Zhao, Yan (2016) Surface-Cross-Linked Micelles as Multifunctionalized Organic Nanoparticles for Controlled Release, Light Harvesting, and Catalysis. Langmuir 32:5703-13

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